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The continuous growth of the current dementia epidemic is contingent on the stability of age- and sex-specific trends over time. However, recent evidence suggests declining or stable trends. The aim of this study was to evaluate the real-world changes in the burden of dementia in older adults in Sweden from 1987 to 2016 by estimating age- and sex-specific incidence of dementia diagnosis in hospital inpatient records (dementia incidence). Differences in trends by sex, age, and educational levels were also examined. The entire Swedish population aged 65 years and older was followed up from 1987 to 2016. Age-, sex-, and education-stratified dementia incidence rates for every follow-up year were estimated using the National Patient Register. Hazard ratio of receiving a dementia diagnosis in the inpatient records per 1 calendar year increase was estimated with discrete time logistic models with a complementary log-log link. After increase, especially in those >85 years of age, dementia incidence started to decrease in the last 5 years of the study period. After 2011, 1 calendar year increase was associated with lower hazard ratio of receiving a hospital diagnosis of dementia. The decrease had the highest magnitude in 70-74-year-olds (-5.5%), followed by 75-79-year-olds (-4.5%) and 80-84-year-olds (-4.0%). The decrease was present in both sexes and at all educational levels up to 90 years of age. Age was associated with the level of dementia incidence, and the trends differed by age group. Educational gradient was observed. University-educated older adults had the lowest rates of dementia. However, the trend over time did not substantially differ by sex or educational level. Our results provide more evidence that dementia incidence may be declining. They also suggest that at least in hospitals, the number of new patients with dementia may decrease in the future.

FLG null variants of which 2282del4 and R501X are the most frequent in Caucasians are established risk factors for atopic dermatitis (AD) with an effect probably mediated through impairment of epidermal barrier. Among subjects with AD FLG defects are also consistently associated with asthma and allergic rhinitis (AR) but it is less clear to what extent these associations are also present independently from skin disease. The aim of the present study was to evaluate the role of 2282del4 and R501X in predisposing to these allergic phenotypes in a Polish population. 2282del4 and R501X were typed among 3,802 participants of the Epidemiology of Allergic Diseases in Poland (ECAP) survey, a cross-sectional population-based study using ECRHS II and ISAAC questionnaires, and ambulatory examination. The FLG null variants were associated with AD (OR = 2.01, CI: 1.20-3.36, P = 0.007), allergic rhinitis (in particular persistent form, OR = 1.69, CI:1.12-2.54, P = 0.011), and asthma (in particular atopic asthma, OR = 2.22, CI:1.24-3.96, P = 0.006). Association with atopic asthma (but not persistent allergic rhinitis) was also present in the absence of AD, (OR = 2.02, CI: 1.07-3.81, P = 0.027) as well as in the absence of AD and history of broadly defined inflammatory skin disease (OR = 2.30, CI: 1.07-4.93, P = 0.03). Association to atopic asthma would have not been found if diagnosis was made by questionnaire only (OR = 1.15, CI: 0.58-2.32, P = 0.8). We did not observe an association between FLG variants and allergic sensitizations (P = 0.8) or total IgE. (P = 0.6). In a Polish population FLG 2282del4 and R501X carriage increases risk for development of AD and atopic asthma (also in the absence of AD or history thereof). This suggests that interventions aimed at restoring epidermal barrier may have a general role in asthma prophylaxis/treatment.

Background Several studies have examined gut microbiota and sarcopenia using 16S ribosomal RNA amplicon sequencing; however, this technique may not be able to identify altered specific species and functional capacities of the microbes. We performed shotgun metagenomic sequencing to compare the gut microbiome composition and function between individuals with and without sarcopenia. Methods Participants were from a community‐based observational study conducted among the residents of rural areas in China. Appendicular skeletal muscle mass was assessed using direct segmental multi‐frequency bioelectrical impedance and grip strength using a Jamar Hydraulic Hand dynamometer. Physical performance was evaluated using the Short Physical Performance Battery, 5‐time chair stand test and gait speed with the 6 m walk test. Sarcopenia and its severity were diagnosed according to the Asian Working Group for Sarcopenia 2019 algorithm. The gut microbiome was profiled by shotgun metagenomic sequencing to determine the microbial composition and function. A gut microbiota‐based model for classification of sarcopenia was constructed using the random forest model, and its performance was assessed using the area under receiver‐operating characteristic curve (AUC). Results The study sample included 1417 participants (women: 58.9%; mean age: 63.3 years; sarcopenia prevalence: 10.0%). β‐diversity indicated by Bray–Curtis distance (genetic level: P = 0.004; taxonomic level of species: P = 0.020), but not α‐diversity indicated by Shannon index (genetic level: P = 0.962; taxonomic level of species: P = 0.922), was significantly associated with prevalent sarcopenia. After adjusting for potential confounders, participants with sarcopenia had higher relative abundance of Desulfovibrio piger (P = 0.003, Q = 0.090), Clostridium symbiosum (P < 0.001, Q = 0.035), Hungatella effluvii (P = 0.003, Q = 0.090), Bacteroides fluxus (P = 0.002, Q = 0.089), Absiella innocuum (P = 0.002, Q = 0.072), Coprobacter secundus (P = 0.002, Q = 0.085) and Clostridium citroniae (P = 0.001, Q = 0.060) than those without sarcopenia. The relative abundance of six species (Desulfovibrio piger, Clostridium symbiosum, Hungatella effluvii, Bacteroides fluxus, Absiella innocuum, and Clostridium citroniae) was also positively associated with sarcopenia severity. A differential species‐based model was constructed to separate participants with sarcopenia from controls. The value of the AUC was 0.852, suggesting that model has a decent discriminative performance. Desulfovibrio piger ranked the highest in this model. Functional annotation analysis revealed that the phenylalanine, tyrosine, and tryptophan biosynthesis were depleted (P = 0.006, Q = 0.071), while alpha‐Linolenic acid metabolism (P = 0.008, Q = 0.094), furfural degradation (P = 0.001, Q = 0.029) and staurosporine biosynthesis (P = 0.006, Q = 0.072) were enriched in participants with sarcopenia. Desulfovibrio piger was significantly associated with staurosporine biosynthesis (P < 0.001). Conclusions This large population‐based observational study provided empirical evidence that alterations in the gut microbiome composition and function were observed among individuals with sarcopenia.

Background In southern Europe, the risk of cancer in patients with end-stage kidney disease receiving dialysis has not been well quantified. The aim of this study was to assess the overall pattern of risk for de novo malignancies (DNMs) among dialysis patients in the Friuli Venezia Giulia region, north-eastern Italy. Methods A population-based cohort study among 3407 dialysis patients was conducted through a record linkage between local healthcare databases and the cancer registry (1998–2013). Person-years (PYs) were calculated from 30 days after the date of first dialysis to the date of DNM diagnosis, kidney transplant, death, last follow-up or December 31, 2013, whichever came first. The risk of DNM, as compared to the general population, was estimated using standardized incidence ratios (SIRs) and 95% confidence intervals (CIs). Results During 10,798 PYs, 357 DNMs were diagnosed in 330 dialysis patients. A higher than expected risk of 1.3-fold was found for all DNMs combined (95% CI: 1.15–1.43). The risk was particularly high in younger dialysis patients (SIR = 1.88, 95% CI: 1.42–2.45 for age 40–59 years), and it decreased with age. Moreover, significantly increased DNM risks emerged during the first 3 years since dialysis initiation, especially within the first year (SIR = 8.52, 95% CI: 6.89–10.41). Elevated excess risks were observed for kidney (SIR = 3.18; 95% CI: 2.06–4.69), skin non-melanoma (SIR = 1.81, 95% CI: 1.46–2.22), oral cavity (SIR = 2.42, 95% CI: 1.36–4.00), and Kaposi’s sarcoma (SIR = 10.29, 95% CI: 1.25–37.16). Conclusions The elevated risk for DNM herein documented suggest the need to implement a targeted approach to cancer prevention and control in dialysis patients.

The present study aimed to compare cancer incidence and trends in survival for children diagnosed in Japan and England, using population‐based cancer registry data. The analysis was based on 5192 children with cancer (age 0‐14 years) from 6 prefectural cancer registries in Japan and 21 295 children diagnosed in England during 1993‐2010. Differences in incidence rates between the 2 countries were measured with Poisson regression models. Overall survival was estimated using the Kaplan–Meier method. Incidence rates for Hodgkin lymphoma, renal tumors and Ewing sarcomas in England were more than twice as high as those in Japan. Incidence of germ cell tumors, hepatic tumors, neuroblastoma and acute myeloid leukemia (AML) was higher in Japan than in England. Incidence of all cancers combined decreased in Japan throughout the period 1993 to 2010, which was mainly explained by a decrease in registration of neuroblastoma in infants. For many cancers, 5‐year survival improved in both countries. The improvement in survival in chronic myeloid leukemia (CML) was particularly dramatic in both countries. However, 5‐year survival remained less than 80% in 2005‐2008 in both countries for AML, brain tumors, soft tissue sarcomas, malignant bone tumors and neuroblastoma (age 1‐14 years). There were significant differences in incidence of several cancers between countries, suggesting variation in genetic susceptibility and possibly environmental factors. The decrease in incidence for all cancers combined in Japan was related to the cessation of the national screening program for neuroblastoma. The large improvement in survival in CML coincided with the introduction of effective therapy (imatinib). For many of childhood cancers, 5‐year survival improved in Japan and England. The improvement in survival in chronic myeloid leukaemia (CML) was particularly dramatic in both countries.

INTRODUCTION To examine the burden and clusters of multimorbidity in association with mild cognitive impairment (MCI), dementia, and Alzheimer's disease (AD)‐related plasma biomarkers among older adults. METHODS This population‐based study included 5432 participants (age ≥60 years); of these, plasma amyloid beta (Aβ), total tau, and neurofilament light chain (NfL) were measured in a subsample (n = 1412). We used hierarchical clustering to generate five multimorbidity clusters from 23 chronic diseases. We diagnosed dementia and MCI following international criteria. Data were analyzed using logistic and linear regression models. RESULTS The number of chronic diseases was associated with dementia (multivariable‐adjusted odds ratio = 1.22; 95% confidence interval [CI] = 1.11 to 1.33), AD (1.13; 1.01 to 1.26), vascular dementia (VaD) (1.44; 1.25 to 1.64), and non‐amnestic MCI (1.25; 1.13 to 1.37). Metabolic cluster was associated with VaD and non‐amnestic MCI, whereas degenerative ocular cluster was associated with AD (p < 0.05). The number of chronic diseases was associated with increased plasma Aβ and NfL (p < 0.05). DISCUSSION Multimorbidity burden and clusters are differentially associated with subtypes of dementia and MCI and AD‐related plasma biomarkers in older adults. Highlights We used hierarchical clustering to generate five clusters of multimorbidity. The presence and load of multimorbidity were associated with dementia and mild cognitive impairment. Multimorbidity clusters were differentially associated with subtypes of dementia and Alzheimer's disease plasma biomarkers.

There is limited evidence for the effects of diet on cardiometabolic profiles during the pubertal transition. We collected repeated measures of diet quality and cardiometabolic risk factors among Mexican youth. This analysis included 574 offspring of the Early Life Exposure in Mexico to Environmental Toxicants (ELEMENT) birth cohort followed up to three time points. Dietary Approaches to Stop Hypertension (DASH), alternate Mediterranean Diet (aMedDiet), and Children’s Dietary Inflammatory Index (C-DIITM) scores were computed from food frequency questionnaires. Higher DASH and aMedDiet scores reflect a higher diet quality, and lower C-DII scores reflect an anti-inflammatory diet. Cardiometabolic risk factors were lipid profile, glucose homeostasis, blood pressure, and waist circumference. Linear mixed models were used between quartiles of each diet score and outcomes. Compared to the first quartile, the fourth DASH quartile was inversely associated with log serum insulin (μIU/mL) [β = −0.19, p = 0.0034] and log-Homeostatic Model Assessment of Insulin Resistance [β = −0.25, p = 0.0008]. Additionally, log serum triglycerides (mg/dL) was linearly associated with aMedDiet score [β = −0.03, p = 0.0022]. Boys in the highest aMedDiet quartile had higher serum high-density lipoprotein cholesterol (mg/dL) [β = 4.13, p = 0.0034] compared to the reference quartile. Higher diet quality was associated with a better cardiometabolic profile among Mexican youth.

Background and Purpose Emerging evidence has linked impaired kidney function with dementia in older adults, but the neuropathological pathways underlying their association remain poorly understood. We sought to examine the relationships of kidney function with dementia and plasma biomarkers in a Chinese rural population. Methods This population‐based study used data from the baseline examination of the Multimodal Interventions to Delay Dementia and Disability in rural China (MIND‐China) cohort (March–September 2018; n = 5715). Kidney function was assessed using estimated glomerular filtration rate (eGFR) based on serum creatinine level. Dementia, Alzheimer's disease (AD) and vascular dementia (VaD) were diagnosed according to the international criteria. Plasma biomarkers were measured using the SIMOA platform in a subsample (n = 1446). Data were analyzed using logistic, general linear, and mediation models. Results Of the 5715 participants, 306 were diagnosed with dementia, including 195 with AD and 100 with VaD. Impaired kidney function (eGFR <60 vs. ≥90 mL/min/1.73 m2) was associated with multivariable‐adjusted odds ratios of 2.24 (95% confidence interval [CI] 1.44–3.46) for all‐cause dementia, 1.85 (1.07–3.18) for AD, and 2.49 (1.16–5.22) for VaD. In the biomarker subsample, impaired kidney function was significantly associated with higher plasma amyloid‐β (Aβ)40 (β‐coefficient = 54.36, 95% CI 43.34–65.39), Aβ42 (β‐coefficient = 3.14, 95% CI 2.42–3.86), neurofilament light chain (β‐coefficient = 10.62, 95% CI 5.62–15.62), and total tau (β‐coefficient = 0.68, 95% CI 0.44–0.91), and a lower Aβ42/Aβ40 ratio (β‐coefficient = −4.11, 95% CI −8.08 to −0.14). The mediation analysis showed that plasma total tau significantly mediated 21.76% of the association between impaired kidney function and AD (p < 0.05). Conclusion Impaired kidney function is associated with dementia and plasma biomarkers among rural‐dwelling older Chinese adults, and the association with AD is partly mediated by plasma biomarkers for neurodegeneration.

Background Adequate cytology is limited by insufficient cytologists in a large‐scale cervical cancer screening. We aimed to develop an artificial intelligence (AI)‐assisted cytology system in cervical cancer screening program. Methods We conducted a perspective cohort study within a population‐based cervical cancer screening program for 0.7 million women, using a validated AI‐assisted cytology system. For comparison, cytologists examined all slides classified by AI as abnormal and a randomly selected 10% of normal slides. Each woman with slides classified as abnormal by either AI‐assisted or manual reading was diagnosed by colposcopy and biopsy. The outcomes were histologically confirmed cervical intraepithelial neoplasia grade 2 or worse (CIN2+). Results Finally, we recruited 703 103 women, of whom 98 549 were independently screened by AI and manual reading. The overall agreement rate between AI and manual reading was 94.7% (95% confidential interval [CI], 94.5%‐94.8%), and kappa was 0.92 (0.91‐0.92). The detection rates of CIN2+ increased with the severity of cytology abnormality performed by both AI and manual reading (Ptrend < 0.001). General estimated equations showed that detection of CIN2+ among women with ASC‐H or HSIL by AI were significantly higher than corresponding groups classified by cytologists (for ASC‐H: odds ratio [OR] = 1.22, 95%CI 1.11‐1.34, P < .001; for HSIL: OR = 1.41, 1.28‐1.55, P < .001). AI‐assisted cytology was 5.8% (3.0%‐8.6%) more sensitive for detection of CIN2+ than manual reading with a slight reduction in specificity. Conclusions AI‐assisted cytology system could exclude most of normal cytology, and improve sensitivity with clinically equivalent specificity for detection of CIN2+ compared with manual cytology reading. Overall, the results support AI‐based cytology system for the primary cervical cancer screening in large‐scale population. This study aims to assess the role of Artificial Intelligence (AI) in the detection of early cervical cancer in a low resource setting. Our results showed that AI‐assisted cytology could identify most of negative cytology, and showed higher positive predictive value for CIN2 or worse when compared with cytologists. This study indicates that AI‐assisted cytology could be very useful tool as a primary screening method in a large‐scale cervical cancer screening program to improve its effectiveness.